A Study of Subcutaneous Mircera in Participants With Chronic Kidney Disease Not Treated With ESA or on Dialysis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Subcutaneous Mircera in Participants With Chronic Kidney Disease Not Treated With ESA or on Dialysis (NCT00559637), a na phase 3 study. The primary outcome is Percentage of Participants With Both Hemoglobin Values of the Evaluation Phase in the Range of 11-12 Grams Per Deciliter (g/dL).

2. Clinical Question

The registry record describes a Phase 3, single-group study of monthly subcutaneous methoxy polyethylene glycol-epoetin beta, also called C.E.R.A. In the official title and Mircera in the study title. Its stated aim was to assess efficacy and safety in people with chronic kidney disease and renal anemia who were not on dialysis and were not yet treated with an erythropoiesis-stimulating agent. The central question was whether participants would meet a prespecified hemoglobin range at both measurements in the evaluation phase. The record also lists outcomes concerning time in hemoglobin ranges, time to a hemoglobin value over 11 g/dL, dose adjustments, and red blood cell transfusions.

The record lists enrollment of 184. It does not report the primary endpoint estimate or its confidence interval, so the posted record does not answer the primary question with a numerical result. This distinction matters: the endpoint definition describes what was intended to be counted, but it is not itself evidence of how many participants met that definition.

3. Trial Design

This was an open, single-group Phase 3 study. The registry lists 184 participants enrolled and identifies methoxy polyethylene glycol-epoetin beta as the study drug. Participants received monthly subcutaneous administration. The brief summary gives an initial weight-based dose of 1.2 micrograms/kilogram, while the arm description says that later dose adjustments depended on hemoglobin values. The arm description states a treatment duration of 9 months for all participants; the brief summary describes an anticipated time on study treatment of 9-11 months.

There was no randomized allocation and no masking. In a single-group study, outcomes observed during treatment are described within the treated group. Without a concurrent control group, changes over time cannot be separated from other explanations using a randomized comparison. This is particularly important when interpreting a clinical outcome: a within-group proportion is not a comparative treatment effect.

The primary endpoint concerned both hemoglobin measurements during the evaluation phase, identified as Months 8 and 9, or Study Days 200-260. The two values had to be at least 21 days apart. A participant was classified as a responder only if both values were in the range of 11-12 g/dL. Transfusion of erythrocytes between Study Day 139 and 260, a missing evaluation value, or a value outside the range led to classification as a non-responder for this hemoglobin-range endpoint.

The registry lists the study as completed, with a start date of 2008-01 and primary completion in 2010-06. These dates describe the registry record; they do not supply outcome results. The record lists 8 outcome measures, including the primary measure and secondary measures on hemoglobin duration, time to a hemoglobin value over 11 g/dL, dose adjustments, and transfusions. No analyses are listed. The protocol’s detailed statistical plan, any interim analyses, and a sample-size justification are not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Intent to treat (ITT) population included all participants who received at least one dose of study medication with at least one hemoglobin value measured during treatment period.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: Safety population included all participants who received at least one dose of study medication.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With Both Hemoglobin Values of the Evaluation Phase in the Range of 11-12 Grams Per Deciliter (g/dL), measured over Evaluation phase (Months 8 and 9).

The primary endpoint is the percentage of participants whose two hemoglobin values in the evaluation phase were both within 11-12 g/dL. The measurements were scheduled in Months 8 and 9, described also as Study Days 200-260, and had to be at least 21 days apart. This is a threshold-based responder endpoint: each participant is classified as either meeting the full rule or not meeting it.

The endpoint also specifies how particular circumstances affect classification. Participants with an erythrocyte transfusion between Study Day 139 and 260, at least one missing evaluation value, or a value outside the target range were counted as non-responders for this endpoint. Thus, the measure is not simply the percentage of available hemoglobin readings that fall in range. It combines the two-measurement requirement with rules for missing values and transfusions.

As a general statistical point, a responder proportion can make a clinical target easier to interpret than a long series of continuous measurements, but it compresses information. It does not show how far values were from the range, how hemoglobin changed between measurements, or how much variability there was among participants. The endpoint can describe the frequency of meeting the specified rule; by itself, it does not establish a comparative effect.

The registry record does not report the percentage meeting the endpoint, the number classified as responders, or the 95% confidence interval. The definition is available, but the result needed to quantify the endpoint is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a binary responder endpoint summarized as a percentage of participants. Each participant is assessed against a rule requiring both evaluation-phase hemoglobin values to lie within 11-12 g/dL. The analysis is therefore based on participant-level classification rather than counting every hemoglobin measurement as a separate observation. The reported unit is percentage of participants, and the specified measure of uncertainty is a 95% confidence interval.

What a responder percentage represents

General statistical explanation: a proportion summarizes the share of a defined group with a specified outcome. Here, the outcome is not simply one hemoglobin result in range; it is meeting the complete two-value rule, including the timing and classification conditions. To interpret such a proportion, readers need both the estimate and its denominator. The registry record does not report the estimate, the number of responders, the confidence interval, or the actual number of participants in the endpoint population.

The record defines its ITT population as participants who received at least one dose of study medication and had at least one hemoglobin value measured during the treatment period. That population definition is not the same as the enrollment total by assumption. The registry lists enrollment of 184, but does not report how many participants met the ITT definition or how many were included in the primary endpoint calculation. The record’s responder rules further classify some missing evaluation values as non-response, but they do not state the counts in each category.

How to read the confidence interval

General statistical explanation: a confidence interval communicates uncertainty around an estimate. A narrower interval indicates greater precision under the method’s assumptions; a wider interval indicates less precision. It is not a guarantee that the true value lies inside the particular interval, nor does it address bias arising from design or measurement. Since the registry gives no primary estimate or interval, readers cannot judge the precision of the primary endpoint from this record.

The registry specifies a 95% confidence interval for the primary measure but does not report the interval method. The record also does not report details of a statistical analysis plan, including whether any adjusted analyses were planned, which covariates might have been used, or how other endpoints were to be analyzed. Those details are not reported in the registry record and should not be inferred from the endpoint label.

Thresholds, missing measurements, and transfusions

The primary endpoint applies a fixed range and two-timepoint rule. General statistical explanation: turning a continuous measurement into a binary outcome can simplify communication, but it discards information about values within each category and about how close a value is to a cutoff. A participant just outside the range and a participant farther away are both non-responders under this rule. The endpoint also treats a missing evaluation measurement as non-response, so its result would reflect both observed values and the prespecified missing-value classification.

The record specifies that participants who received an erythrocyte transfusion between Study Day 139 and 260 were also non-responders for the endpoint. It does not report how many participants had transfusions in that interval. The list of secondary outcomes separately includes total red blood cell transfusions, but no outcome analysis is posted. How missing data were handled for secondary outcomes, and whether any sensitivity analyses were conducted, are not reported in the registry record.

Design and comparison

This is a single-group study with no masking and no randomized allocation. General statistical explanation: randomization supports a fair comparison between groups by assigning treatment independently of participant characteristics, while masking can reduce some forms of knowledge-related influence. Neither feature creates a comparison in this study. A within-group percentage can describe the treated cohort, but it is not a between-group treatment contrast and cannot control for changes or influences outside the treatment.

The sample-size section is a planning illustration computed from the observed effect, not the trial’s own design. Its stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. These assumptions describe a hypothetical two-arm calculation, unlike this single-group trial. Any sample sizes in that section are planning illustrations, never observed power. The registry record does not report the study’s own sample-size justification or the assumptions used when the trial was designed.

The record lists no analyses. It does not report whether interim analyses were conducted, what statistical tests were applied to the primary measure, or whether multiplicity adjustments were made. General statistical explanation: prespecifying methods helps distinguish planned analyses from exploratory ones and can clarify how uncertainty and multiple outcomes are handled. Without those details or posted endpoint results, the calculation choices and interpretation of the primary result cannot be independently assessed from this record.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Methoxy Polyethylene Glycol-epoetin Beta")
n      <- c(178)
events <- c(19)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Methoxy Polyethylene Glycol-epoetin Beta  178  19  10.7  6.6  16.2  6.9  16.1  7.0  16.1

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 8 outcome measures, including the primary endpoint and secondary measures concerning the duration of hemoglobin values in specified ranges, time to a hemoglobin value over 11 g/dL, dose adjustments, and red blood cell transfusions. It lists no analyses. The record therefore does not show which secondary outcomes were analyzed, what estimates were obtained, or whether any adjustment for multiple outcome testing was used.

General statistical explanation: examining multiple outcomes can increase the chance that at least one result appears notable by chance, depending on the testing strategy. A multiplicity plan may identify a primary outcome, define an order for testing, or adjust interpretation across outcomes. The registry record identifies a primary outcome but does not report a multiplicity procedure or enough analysis details to determine how the multiple listed outcomes were treated.

The primary endpoint includes explicit rules for missing measurements: at least one missing evaluation-phase value results in non-responder classification. It also classifies participants with a transfusion in the specified period or an out-of-range value as non-responders. The record does not report how many participants were affected by each rule. It also does not report whether sensitivity analyses examined alternative missing-data assumptions.

The ITT population is defined as participants who received at least one dose and had at least one hemoglobin value measured during treatment. The number meeting this definition, the number excluded from it, and the endpoint denominator are not reported in the registry record. The recorded enrollment of 184 should not be substituted for an unreported analysis population. The handling of missing data for secondary endpoints is also not reported in the registry record.

As a general matter, missing-data rules are part of an endpoint’s meaning: counting a missing value as non-response gives a different interpretation from analyzing only observed measurements. Here, the rule is stated, but the frequency of missingness and its effect on the result cannot be evaluated without the participant counts and primary estimate.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: renal failure (14.7%), nephrogenic anaemia (6.5%), renal failure chronic (4.3%), haemorrhagic anaemia (3.3%), renal impairment (2.7%).

The safety listing reports 184 participants at risk for serious adverse events and 88 affected. It also reports 184 at risk for other adverse events and 109 affected. These are counts of participants in the treatment group, not evidence by themselves that the study drug caused an event. The record does not include a concurrent control group against which to compare these counts.

The registry lists selected serious adverse event terms with percentages: Renal failure, 14.7%; Nephrogenic anaemia, 6.5%; Renal failure chronic, 4.3%; Haemorrhagic anaemia, 3.3%; Renal impairment, 2.7%; and Shunt occlusion, 2.7%. The denominator and precise calculation basis for these term percentages are not reported in the registry record. The terms may not represent mutually exclusive groups, so they should not be added together or treated as a total.

The deaths field is not populated with a value, so deaths are not reported in the registry record. The safety figures do not establish causation, comparative risk, or the clinical seriousness of an individual participant’s course. They are descriptive entries for this single-group study, and the record does not provide a randomized safety comparison.

13. What the Result Does, and Does Not, Mean

The result this study’s primary endpoint was designed to summarize is clear in definition: the percentage of participants whose two evaluation-phase hemoglobin values were both in the range of 11-12 g/dL, subject to the stated timing and non-responder rules. But the registry record does not report the primary endpoint estimate, the responder count, or its 95% confidence interval. The posted record therefore does not allow readers to say how frequently participants met the endpoint or how precisely that frequency was estimated.

The record does show the study’s design and treatment approach. It was an open, single-group Phase 3 study, with monthly subcutaneous injections and a starting dose of 1.2 mcg/kg, followed by dose adjustments depending on hemoglobin values. It lists enrollment of 184. The ITT population, however, is defined by treatment exposure and a measured hemoglobin value, and the number meeting that definition is not reported.

Even if a primary responder proportion were available, a single-group result would remain descriptive. General statistical explanation: without a concurrent comparator, an outcome observed during treatment cannot be interpreted as a randomized estimate of the difference between treatment and control. The design does not support a like-for-like comparison, and the record should not be read as showing a causal effect simply because an outcome was measured after treatment began.

The safety listing reports serious and other adverse event counts and selected serious-event terms. Those entries describe events recorded in the study group. They do not, on their own, show whether an event was caused by treatment or how event frequency compares with another group. The deaths value is not reported in the registry record.

The secondary outcome list indicates additional questions the study intended to address, including time spent in hemoglobin ranges, time to a value over 11 g/dL, dose adjustments, and transfusions. The registry record does not report analyses for these outcomes. Overall, the record supports a description of the design, endpoint rules, and listed safety data, but not a numerical conclusion about the primary endpoint or a comparative treatment effect.

14. Why This Trial Matters Statistically

This trial is statistically instructive because its endpoint definition is more specific than a simple statement that hemoglobin was measured. A participant had to have both evaluation-phase values in the 11-12 g/dL range, with the values at least 21 days apart. The classification also treats missing values, values outside the range, and transfusions in the stated period as non-response. These details show how a clinical question becomes an operational outcome that can be counted.

The design makes the boundary between description and comparison especially important. This was a single-group study, with no randomized allocation and no masking. A percentage from the treated cohort could describe the frequency of meeting the endpoint, but it would not be a randomized contrast with another group. Readers need to keep that distinction in view when interpreting any posted table or plot.

The registry record also illustrates why endpoint definitions and endpoint results must be considered separately. The record supplies a detailed primary endpoint rule and names a 95% confidence interval, yet it does not report the estimate or interval. A clear definition helps explain what a result would mean; it cannot replace the absent result or its uncertainty.

Finally, the study’s safety listings are descriptive. The counts and serious-event terms provide information about events recorded in the study group, but there is no comparator to support a relative safety estimate. The record lists multiple outcomes and no analyses, so the statistical handling of multiple endpoints is not visible. Taken together, these features make the study useful for understanding how design, endpoint rules, missingness, and reporting completeness affect what readers can conclude from a registry record.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The most important limitation for interpreting this registry record is that it does not report the primary endpoint result. The responder percentage, responder count, confidence interval, and actual primary analysis population are absent. Thus, the study’s central efficacy measure cannot be quantified from the posted record.

The single-group, open design has no randomized comparator and no masking. A within-group outcome cannot provide a randomized comparison, and the safety counts cannot be compared with a control group in this record. The design also means that descriptive outcomes should not be presented as proof of causation.

The endpoint uses two measurements in a defined evaluation period, while missing values, out-of-range values, and transfusions in a stated period are classified as non-response. However, the record does not report how many participants fell into these categories. The ITT definition is given, but the number of participants meeting it is not reported. Enrollment of 184 is not a substitute for the unreported endpoint denominator.

The record lists 8 outcome measures but no analyses. It does not report the statistical analysis plan, multiplicity handling, interim analyses, sensitivity analyses, or methods for secondary outcomes. The sample-size justification used for the trial is not reported in the registry record. The sample-size section is a planning illustration based on stated hypothetical two-arm assumptions, not an account of the trial’s original design or observed power.

Safety interpretation is also limited: the record lists counts and selected serious-event terms, but does not report the deaths value or the denominator and calculation basis for the term percentages. These limitations restrict what can be concluded from the registry record beyond its design, endpoint definitions, and posted descriptive safety entries.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study of Subcutaneous Mircera in Participants With Chronic Kidney Disease Not Treated With ESA or on Dialysis — NCT00559637.
• Registry record last updated 2016-04-06; status last verified 2016-03.
• Results first posted 2016-04-06.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

This completed Phase 3 study was an open, single-group investigation of monthly subcutaneous methoxy polyethylene glycol-epoetin beta in participants with chronic kidney disease and anemia. The registry lists enrollment of 184, a start date of 2008-01, and primary completion in 2010-06.

The primary endpoint was the percentage of participants with both evaluation-phase hemoglobin values in the range of 11-12 g/dL, with missing values, out-of-range values, and specified transfusions classified as non-response. The registry record does not report the primary endpoint estimate or its 95% confidence interval. It lists 8 outcome measures and no analyses.

The safety section reports 88 participants with serious adverse events and 109 with other adverse events, each among 184 at risk. Selected serious-event terms are listed with percentages; deaths are not reported in the registry record. The single-group design does not provide a randomized comparison.